The present invention relates to a microelement, device having a plurality of microelements, arranged on a substrate, for making contact to cells present in a liquid, preferably biological environment.
The invention further relates to a method for making contact to cells present in a liquid, preferably biological, environment above a substrate, in which a contact is created between the cells and microelements.
Lastly, the invention relates to a method for manufacturing a microelement device having a plurality of microelectrodes, in which the microelements are arranged on a substrate.
It is known to use so-called microelectrode devices for the investigation of biological cells. The microelectrode electrodes serve in this context, for example, to stimulate the cells or to sense potentials. The investigations can be conducted in a biological environment or in an artificial environment. This can be, for example, a suspension having artificial vesicles made of lipids, pores being incorporated into the vesicle shell as a model system for biological cells. For this purpose the arrangements comprise, on a substrate, a plurality of microelectrodes whose dimensions are of approximately the order of magnitude of the cells, i.e. in the range from a few μm to several tens of μm.
German Patent Application P 195 29 371, of earlier priority but not previously published, discloses a microelectrode device of this kind.
To measure bioluminescence or chemoluminescence, e.g. as a reaction to chemical stimulus (toxins, drugs), and to measure changes in light absorption caused by such a stimulus when a light source is used above the cells, it is possible to utilize light-sensitive microelements, for example microphotodiodes, which are sensitive to specific spectral regions.
Microelectrodes, microphotodiodes, and the like are referred to globally, in the context of the present invention, as “microelements.”
The following problems, inter alia, arise with microelectrode arrangements of conventional type and with the methods carried out therewith:
When the microelement device is brought into contact with a suspension, i.e. a liquid, for example biological, environment in which cells are present, it is more or less a matter of chance whether one cell or another settles on a specific electrode. In practice, the cells can generally be caused to settle on an electrode only with partial coverage, so that stimulation of the cell or sensing of a cell potential is confined to that partial surface. When the cell is stimulated, for example, a portion of the stimulation energy is lost in the suspension which acts as the electrolyte.
In addition, the cells only rest loosely on the electrodes. This can result in problems in terms of sealing resistance with respect to the reference electrode. In addition, the contact is very sensitive and is disrupted in response to even extremely small mechanical influences, since the cells detach from the contact.